title: Pattern of retinal ganglion cell loss in dominant optic atrophy due to OPA1 mutations.
abstract: OBJECTIVE
  The majority of patients with autosomal dominant optic atrophy (DOA) harbour pathogenic OPA1 mutations. Although DOA is characterised by the preferential loss of retinal ganglion cells (RGCs), about 20% of patients with OPA1 mutations will develop a more severe disease variant (DOA+), with additional neuromuscular features. In this prospective, observational case series, optical coherence tomography (OCT) was used to define the pattern of retinal nerve fibre layer (RNFL) loss in patients with both the pure and syndromal forms of DOA.
  
  
  METHODS
  Forty patients with a molecular diagnosis of DOA due to OPA1 mutations were prospectively recruited from our neuro-ophthalmology clinic: 26 patients with isolated optic atrophy and 14 patients manifesting DOA+ features. Peripapillary RNFL thickness was measured with the Fast RNFL (3.4) acquisition protocol on a Stratus OCT.
  
  
  RESULTS
  There was a statistically significant reduction in average RNFL thickness in the OPA1 group compared with normal controls (P<0.0001). The percentage decrease was greatest in the temporal quadrant (59.0%), followed by the inferior (49.6%), superior (41.8%), and nasal (25.9%) quadrants. Patients with DOA+ features had worse visual outcomes compared with patients with pure DOA. Except in the temporal quadrant, RNFL measurements were significantly thinner for the DOA+ group. There was an inverse correlation between average RNFL thickness and logarithm of the minimum angle of resolution (LogMAR) visual acuity (P<0.0001).
  
  
  CONCLUSIONS
  RGC loss in DOA is characterised by severe involvement of the temporal papillomacular bundle, with relative sparing of the nasal fibres. RNFL thinning is more pronounced in patients with DOA+ phenotypes.
authors.affiliation: Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK. Patrick.Yu-Wai-Man@ncl.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Yu-Wai-Man
authors.forename: M
authors.initials: M
authors.lastname: Bailie
authors.forename: A
authors.initials: A
authors.lastname: Atawan
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: P G
authors.initials: PG
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology; D011446:Prospective Studies; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human